The face distinguishes one human being from another. When the face is disfigured from injuries, tumor resection, congenital anomalies or infectious diseases, the patient experiences both physical and psychosocial trauma, and therefore has strong desire for both functional and esthetic reconstruction. In the past decade, tissue engineering of orofacial structures has provided the proof of concept that single tissue fragments, such as dentin and bone, can regenerate in vitro or in small animal models. However, patients with dental pulp infection need the regeneration of both dentin and dental pulp;patients with deep facial defects can only be healed not only by the regeneration of bone, but also the overlaying, vascularized soft tissue that is attached to bone. We take advantage of the GO grant mechanism to assemble an existing critical mass of and well established scientists and multi-disciplinary surgeons into a consortium to regenerate dental pulp-dentin grafts and facial soft tissue-bone grafts in a pre-clinical, large animal model. Dental caries and trauma involving the dental pulp-dentin complex is the pillar of dental practice, with a current volume over 24 million procedures or ~30 billion dollars annually in the United States alone. Regenerated pulp-dentin grafts will transform this segment of dental practice. In parallel, biologically regenerated facial soft tissue-bone grafts will eliminate the need for autologous tissue grafting, and transform multiple clinical disciplines including Oral &Maxillofacial Surgery, Otolaryngology/Head and Neck Surgery, and Plastic and Reconstructive Surgery. Our existing multi-disciplinary expertise in stem cell biology, materials science, chemical engineering, mechanical engineering, cell and molecular biology, animal surgery and clinical knowledge will continue to advance the regeneration of clinically relevant orofacial tissues into Phase I human clinical trials upon the completion of the present two-year GO grant. With assistance of a FDA consultant who has previously worked with the PIs, we will plan for first-in- human clinical trials on dental pulp-dentin grafts and facial soft tissue-bone grafts in the present GO grant. PUBLIC HEALTH RELEVANCE: We take advantage of the GO grant mechanism to assemble an existing critical mass of well established scientists and multi-disciplinary surgeons into a consortium to regenerate dental pulp-dentin grafts and facial soft tissue-bone grafts in a pre-clinical, large animal model. With assistance of a FDA consultant who has previously worked with the PIs, we will plan for first-in-human clinical trials on dental pulp-dentin grafts and facial soft tissue-bone grafts in the present GO grant.